This comprehensive research study delves into the structural relaxation of micronized Fluticasone Propionate (FP) under various lagering conditions and its subsequent influence on the aerodynamic particle size distribution (APSD) of binary and tertiary carrier-based dry powder inhaler (DPI) formulations. The study meticulously investigates the changes in physicochemical, surface interfacial properties, and amorphous disorder levels of FP samples under different conditions. The findings suggest that environmental conditions during the lagering of FP can significantly impact its physicochemical and interfacial properties, thereby influencing the performance of binary and tertiary carrier-based dry powder inhaler formulations. This research provides valuable insights and a deeper understanding of the process-induced structural disorder, particle adhesion, and mechanical activation, which are crucial in the pharmaceutical industry.